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NAD and Cognition by Dr Surya Teja

NAD and Cognition by Dr Surya Teja



NAD+ is an essential metabolite for life andhealth because it has anti-inflammatory effects, and aids in stem cellrejuvenation, autophagy, nuclear–mitochondrial communication, and cellular resilienceand survival. It also plays a role in numerous known cellular reactions thataffect redox status, energy production, and metabolic homeostasis.(1)


Decreased levels of NAD+ are crucial for brainaging and neurodegenerative diseases because NAD+ replenishment enhancesmitochondrial biogenesis and function and reduces the build-up of damagedmitochondria in models of Alzheimer's disease (AD) and premature aging. A decline in NAD+ levels in the brain tissues of aged normal mice andanimals with accelerated aging is linked to the age-related decrease in theproduction of mitochondria.(2) Variousmechanisms have been suggested to account for the neuroprotective effects ofsupplementing NAD+ levels. Evidence derived from various contexts suggests thatthese mechanisms include decreased oxidative stress, lowered proteinaggregation, anti-inflammatory effects, blocking autophagy, and reduction ofmitochondrial damage and dysfunction. Based on these findings, theunderlying pathway is multiple and complex. (3)


The steady decrease in NAD+levels seen in several tissues, including the brain, is one of thecharacteristics of aging. Numerous mechanisms have been linked to this drop,including reduced biosynthesis, increased consumption by enzymes that consumeNAD+, and poor recycling of NAD+ precursors. Age-related decreases in NAD+levels impair cells' ability to effectively repair DNA damage, which causes anaccumulation of unrepaired DNA lesions. (4) Since neurons have a high metabolic activityand are post-mitotic, they are especially susceptible to DNA damage. DNA damageaccumulation in neurons can lead to neurodegenerative illnesses includingAlzheimer's, Parkinson's, and Huntington's by impairing synaptic transmissionand upsetting cellular function. Age-related decreases in NAD+ levels mayhasten the cognitive decline linked to these disorders and worsen damage toneurons' DNA. (5)


The sirtuinsare a family of proteins that regulate cellular processes like metabolism, aging,and stress response. NAD+ is a coenzyme that is necessary for their action.Sirtuins have been linked to neuroprotection and cognitive function;NAD+-induced sirtuin activation may contribute to the maintenance of cognitivehealth. (6) NAD+ and sirtuins have been implicated in neuroprotectionagainst various insults, including oxidative stress, inflammation, and proteinmisfolding. Activation of sirtuins has been shown to enhance neuronal survivaland protect against neurodegenerative diseases such as Alzheimer's andParkinson's disease.


Nicotinamide adenine dinucleotide (NAD+), which affects sirtuinactivation, DNA repair, and mitochondrial health, is necessary to maintaincognitive function. With treatments that aim to raise NAD+ levels, there ishope for preserving cognitive health and possibly preventing age-relatedcognitive decline. Taking NAD precursor supplements, like NMN, and getting NAD+infusion are few practices to improve NAD+ levels.




1.              Lautrup S, Hou Y, Fang EF, BohrVA. Roles of NAD+ in Health and Aging. Cold Spring Harb Perspect Med. 2024 Jan1;14(1):a041193.

2.              Lautrup S, SinclairDA, Mattson MP, Fang EF. NAD+ in Brain Aging and Neurodegenerative Disorders.Cell Metabolism. 2019 Oct;30(4):630–55.

3.              Campbell JM.Supplementation with NAD+ and Its Precursors to Prevent Cognitive Declineacross Disease Contexts. Nutrients. 2022 Jan;14(15):3231.

4.              Mouchiroud L,Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C, et al. The NAD(+)/SirtuinPathway Modulates Longevity through Activation of Mitochondrial UPR and FOXOSignaling. Cell. 2013 Jul 18;154(2):430–41.

5.              Aging and NeuronalVulnerability - PMC [Internet]. [cited 2024 May 10]. Available from:

6.              Fagerli E, EscobarI, Ferrier FJ, Jackson CW, Perez-Lao EJ, Perez-Pinzon MA. Sirtuins andcognition: implications for learning and memory in neurological disorders.Front Physiol. 2022;13:908689.